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Triglycerides (TG also triacylglycerol, TAG, or triacylglyceride) are neutral esters of glycerol. Instead of hydroxyl groups, there are chains of three fatty acids. In fact, glycerol is an alcohol consisting of a chain of three carbon atoms (C) with a hydroxyl group (OH) attached to each carbon atom. Fatty acids are joined to the alcohol by ester bonds following a condensation reaction, with the elimination of one molecule of water (H2O) for each fatty acid.
Triglycerides are part of the glyceride family along with monoglycerides and diglycerides. They make up an important part of vegetable oil and animal fat. Triglycerides make up a large part (90-98 %) of the fats or lipids contained in food and in the human body.
Triacylglycerols are produced in animal tissues from two precursors (acyl-CoA and L-glycerol 3-phosphate) by a series of enzymatic reactions. Glycerol 3-phosphate can be formed in two ways. It can be derived from dihydroxyacetone phosphate produced in glycolysis by the action of the NAD-dependent glycerol 3-phosphate dehydrogenase located in the cytosol, whereas in the kidney and liver it can be formed from glycerol by phosphorylation catalyzed by glycerol kinase.
The other precursors of triacylglycerols are acyl-CoA, which is formed from fatty acids by acyl-CoA synthetase, the same enzyme that activates fatty acids to enter β-oxidation. The first step in the synthesis of triacylglycerols is the acylation of the two free hydroxyl groups of L-glycerol 3-phosphate with two molecules of acyl-CoA to generate diacylglycerol 3-phosphate, better known as phosphatidic acid or phosphatidate. In the pathway leading to the formation of triacylglycerols, phosphatidate is hydrolyzed by phosphatidate phosphatase to form 1,2-diacylglycerol. The diacylglycerols can be converted to triacylglycerols by transesterification with a third acyl-CoA molecule.
Triglycerides are tri-esters consisting of a glycerol bound to three fatty acid molecules. Alcohols have a hydroxyl (HO–) group. Organic acids have a carboxyl (–COOH) group. Alcohols and organic acids join to form esters. The glycerol molecule has three hydroxyl (HO–) groups and each fatty acid has a carboxyl group (–COOH). In triglycerides, the hydroxyl groups of the glycerol join the carboxyl groups of the fatty acid to form ester bonds:
HOCH2CH(OH)CH2OH + RCO2H + R′CO2H + R″CO2H → RCO2CH2CH(O2CR′)CH2CO2R″ + 3H2O
The three fatty acids (RCO2H, R′CO2H, R″CO2H in the above equation) are usually different, as many kinds of triglycerides are known. The length of fatty acid chains in common triglyceride structures can be from 5 to 28 carbon atoms, but 17 and 19 are more common. Shorter chains can be detected in some substances (butyric acid in butter). Natural fatty acids found in plants and animals are typically composed of only even numbers of carbon atoms, reflecting the pathway for their biosynthesis from the two-carbon building-block acetyl CoA. Bacteria, however, possess the ability to synthesise odd- and branched-chain fatty acids. As a result, ruminant animal fat contains odd-numbered fatty acids, such as 15, due to the action of bacteria in the rumen. Many fatty acids are unsaturated; some are polyunsaturated (e.g., those derived from linoleic acid).
Most natural fats contain a complex mixture of individual triglycerides. Because of this, they melt over a broad range of temperatures. Cocoa butter is unusual in that it is composed of only a few triglycerides, derived from palmitic, oleic, and stearic acids in the 1-, 2-, and 3-positions of glycerol, respectively.
However, fats cannot be dissolved in water; for this reason their transport in the circulation is entrusted to particular “bipolar carriers”, called lipoproteins. The first, synthesized by enterocytes, are the chylomicrons. These have the purpose of transporting triglycerides, initially through the lymph and then through the blood, from the intestine to the tissues – the exchange between the two circulations (from lymphatic to blood) takes place in the thoracic duct.
In the blood, chylomicrons interact with other lipoproteins (HDL and LDL), which allow them to fully perform their functions and complete the metabolic cycle. When they reach the tissues, chylomicrons release triglycerides that, through the work of specific enzymes called lipoprotein lipase, are broken down again into glycerol and fatty acids. These nutrients will then be used to meet the energy needs of the cell or deposited within the adipose tissue (see below).
The liver also has the ability to synthesize triglycerides, starting from other nutrients such as glucose (this explains why a diet rich in simple sugars is often correlated with an increase in triglyceridemia) and amino acids. Once produced, these triglycerides are bundled with specific lipoproteins called VLDLs (similar to chylomicrons but a bit poorer in triglycerides and rich in cholesterol and protein) that will transport them to tissues through the bloodstream.
The entry into the cells of triglycerides is facilitated by the presence of insulin and it is also for this reason that in diabetics are more frequent cases of dyslipidemia (alteration of the amount of fat or lipids normally present in the blood).
Triglycerides, hydrolyzed “enzymatically” into fatty acids + glycerol (by a lipase), contain one of the three most important energy substrates in the body. Fatty acids are the main source of kilocalories, providing 9 per gram, while glycerol is recovered by the liver for neoglucogenesis – glucose synthesis. All this requires oxygen and most of the processes take place in the mitochondrion (mitochondrial oxidation through beta oxidation and Krebs cycle).
In the animal organism, triglycerides are the main elements of adipose tissue, in which they are accumulated within cells called adipocytes – about 87% of adipose is “true fat”.
Adipose tissue is divided into white and brown. The first performs functions of: energy reserve – 1 kg of adipose tissue can provide 7000 kcal – thermo-insulation, mechanical and endocrine cushioning (adiponectin, leptin, estradiol, resistin and cytokines, especially TNFα and interleukin 6, etc). The second, on the other hand, has the role of thermogenesis.
To know the level of circulating triglycerides (triglyceridemia) is sufficient to undergo a blood test. In order to have a reliable value of triglyceridemia it is advisable to keep fasting in the 12 hours preceding the collection and take a light meal the night before.
The triglyceridemia is generally included, in healthy subjects, between 50 and 150 mg/dl (milligrams per deciliter). The “optimal” value is considered to be below 100 mg/dl. Specifically:
- triglycerides below 150 mg/dl are considered “normal”
- triglycerides between 150 and 200 mg/dl are considered “at the limit” (borderline)
- between 200 and 400 mg/dl are considered “high”.
- over 400 mg/dl are considered “very high”.
In order to evaluate in a more complete way the cardiovascular risk of a subject, the determination of triglyceride levels is combined with that of total cholesterol and its fractions (HDL cholesterol and LDL cholesterol, more commonly known as “good” and “bad” cholesterol respectively).
Causes of high triglycerides
It is common that high triglycerides are associated with other typical elements of dyslipidemia – such as total cholesterol and LDL cholesterol above the norm. This is because among the causes and predisposing factors of hypertriglyceridemia are: obesity, hypercaloric and hyperglucidic diet, diabetes mellitus type 2, sedentariness and alcoholism – with the exception of the last one, all elements that participate in the general metabolic decompensation.
In the vast majority of cases, therefore, this condition is due to incorrect lifestyle habits, often associated with altered body composition and loss of general metabolic efficiency.
The cases of familial hypertriglyceridemia (i.e. linked to hereditary factors) are very low (about one case out of a thousand) as well as those related to a deficit in the action of protein lipase (about one case out of a million) or to pathological conditions of the pancreas or kidneys.
Summarizing the most important predisposing factors of hypertriglyceridemia we find therefore:
- sedentariness/reduced physical activity;
- incorrect dietary habits;
- hypercaloric diet;
- hyperglucidic diet;
- diabetes mellitus type 2;
- alcohol abuse;
- nephrotic syndrome (kidney disease);
- Iatrogenic causes (chronic therapy with glucocorticoids, birth control pills, estrogens, some diuretics and some antifungal agents.
The simple correction of these risk factors allows, in most cases, to bring the level of triglycerides in the blood back to normal values. An appropriate lifestyle and some physical activity are therefore effective in both preventing and treating this dangerous condition.